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2-Mercaptonicotinoyl glycine, a new potent melanogenesis inhibitor, exhibits a unique mode of action while preserving melanocyte integrity 2-Mercaptonicotinoyl glycine 是一种新型的强效黑色素生成抑制剂,在保持黑色素细胞完整性的同时,还展现出独特的作用模式。
IF 4.3 3区 医学 Q1 Medicine Pub Date : 2024-04-01 DOI: 10.1111/pcmr.13168
Peggy Sextius, Emilie Warrick, Amélie Prévot-Guéguiniat, Guillaume Lereaux, Florence Boirre, Ludwig Baux, Safa Ben Hassine, Jie Qiu, Xiaoming Huang, Jinzhu Xu, Sébastien Grégoire, Shosuke Ito, Kazumasa Wakamatsu, Xavier Marat

Research on new ingredients that can prevent excessive melanin production in the skin while considering efficacy, safety but also environmental impact is of great importance to significantly improve the profile of existing actives on the market and avoid undesirable side effects. Here, the discovery of an innovative technology for the management of hyperpigmentation is described. High-throughput screening tests on a wide chemical diversity of molecules and in silico predictive methodologies were essential to design an original thiopyridinone backbone and select 2-mercaptonicotinoyl glycine (2-MNG) as exhibiting the most favorable balance between the impact on water footprint, skin penetration potential and performance. The effectiveness of 2-MNG was confirmed by topical application on pigmented reconstructed epidermis and human skin explants. In addition, experiments have shown that unlike most melanogenesis inhibitors on the market, this molecule is not a tyrosinase inhibitor. 2-MNG binds to certain melanin precursors, preventing their integration into growing melanin and leading to inhibition of eumelanin and pheomelanin synthesis, without compromising the integrity of melanocytes.

研究既能防止皮肤黑色素过度生成,又能兼顾功效、安全性和环境影响的新成分,对于显著改善市场上现有活性成分的特性和避免不良副作用具有重要意义。本文介绍了一种用于色素沉着治疗的创新技术。在对多种化学分子进行高通量筛选测试和采用硅学预测方法的基础上,设计出了一种独创的巯基吡啶酮骨架,并筛选出了 2-巯基烟酰甘氨酸(2-MNG),它在水足迹影响、皮肤渗透潜力和性能之间实现了最有利的平衡。在色素重建表皮和人体皮肤外植体上的局部应用证实了 2-MNG 的有效性。此外,实验还表明,与市场上大多数黑色素生成抑制剂不同,这种分子不是酪氨酸酶抑制剂。2-MNG 与某些黑色素前体结合,阻止它们整合成生长中的黑色素,从而抑制黑色素和嗜黑色素的合成,而不会损害黑色素细胞的完整性。
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引用次数: 0
Characterization of PRAME immunohistochemistry reveals lower expression in pediatric melanoma compared to adult melanoma PRAME 免疫组化的特征显示,与成人黑色素瘤相比,小儿黑色素瘤中的 PRAME 表达较低。
IF 4.3 3区 医学 Q1 Medicine Pub Date : 2024-03-20 DOI: 10.1111/pcmr.13167
Stephan Forchhammer, Valentin Aebischer, Daniela Lenders, Christian M. Seitz, Christopher Schroeder, Alexandra Liebmann, Michael Abele, Hannah Wild, Ewa Bien, Malgorzata Krawczyk, Dominik T. Schneider, Ines B. Brecht, Lukas Flatz, Matthias Hahn

Pediatric melanomas are rare tumors that have clinical and histological differences from adult melanomas. In adult melanoma, the immunohistochemical marker PRAME is increasingly employed as a diagnostic adjunct. PRAME is also under investigation as a target structure for next-generation immunotherapies including T-cell engagers. Little is known about the characteristics of PRAME expression in pediatric melanoma. In this retrospective study, samples from 25 pediatric melanomas were compared with control groups of melanomas in young adults (18–30 years; n = 32), adult melanoma (>30 years, n = 30), and benign melanocytic nevi in children (0–18 years; n = 30) with regard to the immunohistochemical expression of PRAME (diffuse PRAME expression >75%/absolute expression). Pediatric melanomas show lower diffuse PRAME expression (4%) and lower absolute PRAME expression (25%) compared to young adult melanomas (15.6%/46.8%) and adult melanomas (50%/70%). A significant age-dependent expression could be observed. An analysis of event-free survival shows no prognostic role for PRAME in pediatric melanoma and young adult melanoma, but a significant association with diffuse PRAME expression in adulthood. The age dependency of PRAME expression poses a potential pitfall in the diagnostic application of melanocytic tumors in young patients and may limit therapeutic options within this age group. The immunohistochemical expression of the tumor-associated antigen PRAME is an increasingly important diagnostic marker for melanocytic tumors and is gaining attention as a possible immunotherapeutic target in melanoma. As the available data primarily stem from adult melanoma, and given the clinical and histological distinctions in pediatric melanomas, our understanding of PRAME expression in this specific patient group remains limited. The age-dependent low PRAME expression shown here constrains the use of this marker in pediatric melanoma and may also limit the use of immunotherapeutic strategies against PRAME in young patients.

小儿黑色素瘤是一种罕见的肿瘤,在临床和组织学上与成人黑色素瘤有所不同。在成人黑色素瘤中,免疫组化标记物 PRAME 越来越多地被用作辅助诊断手段。PRAME 还被研究用作下一代免疫疗法(包括 T 细胞诱导剂)的靶结构。人们对小儿黑色素瘤中 PRAME 的表达特点知之甚少。在这项回顾性研究中,我们将 25 例小儿黑色素瘤样本与对照组的年轻成人黑色素瘤(18-30 岁,n = 32)、成人黑色素瘤(>30 岁,n = 30)和儿童良性黑素细胞痣(0-18 岁,n = 30)的 PRAME 免疫组化表达(弥漫 PRAME 表达 >75%/绝对表达)进行了比较。与年轻成人黑色素瘤(15.6%/46.8%)和成人黑色素瘤(50%/70%)相比,小儿黑色素瘤的PRAME弥漫表达较低(4%),PRAME绝对表达较低(25%)。可以观察到明显的年龄依赖性表达。对无事件生存期的分析表明,PRAME在小儿黑色素瘤和年轻成人黑色素瘤中没有预后作用,但在成年黑色素瘤中与PRAME的弥漫表达有显著关联。PRAME 表达的年龄依赖性给年轻患者黑色素细胞肿瘤的诊断应用带来了潜在的隐患,并可能限制该年龄组患者的治疗选择。肿瘤相关抗原 PRAME 的免疫组化表达是一种日益重要的黑色素细胞肿瘤诊断标志物,并作为黑色素瘤的一种可能免疫治疗靶点而受到越来越多的关注。由于现有数据主要来源于成人黑色素瘤,而儿科黑色素瘤在临床和组织学上存在差异,因此我们对PRAME在这一特殊患者群体中表达情况的了解仍然有限。本文所显示的与年龄相关的低PRAME表达限制了这一标记物在小儿黑色素瘤中的应用,也可能限制了针对PRAME的免疫治疗策略在年轻患者中的应用。
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引用次数: 0
The metabolism of melanin synthesis—From melanocytes to melanoma 黑色素合成的新陈代谢--从黑色素细胞到黑色素瘤。
IF 4.3 3区 医学 Q1 Medicine Pub Date : 2024-03-06 DOI: 10.1111/pcmr.13165
Marelize Snyman, Rachel Elizabeth Walsdorf, Sophia Nicole Wix, Jennifer Gibson Gill

Melanin synthesis involves the successful coordination of metabolic pathways across multiple intracellular compartments including the melanosome, mitochondria, ER/Golgi, and cytoplasm. While pigment production offers a communal protection from UV damage, the process also requires anabolic and redox demands that must be carefully managed by melanocytes. In this report we provide an updated review on melanin metabolism, including recent data leveraging new techniques, and technologies in the field of metabolism. We also discuss the many aspects of melanin synthesis that intersect with metabolic pathways known to impact melanoma phenotypes and behavior. By reviewing the metabolism of melanin synthesis, we hope to highlight outstanding questions and opportunities for future research that could improve patient outcomes in pigmentary and oncologic disease settings.

黑色素的合成需要成功协调细胞内多个区室(包括黑色素体、线粒体、ER/高尔基体和细胞质)的代谢途径。虽然色素的生成可以保护人体免受紫外线的伤害,但这一过程也需要合成代谢和氧化还原的需求,而黑色素细胞必须对这些需求进行精心管理。在本报告中,我们对黑色素代谢进行了最新综述,包括利用代谢领域的新技术和新科技获得的最新数据。我们还讨论了黑色素合成的许多方面,这些方面与已知会影响黑色素瘤表型和行为的代谢途径存在交叉。通过回顾黑色素合成的新陈代谢过程,我们希望强调一些悬而未决的问题和未来研究的机会,从而改善色素性和肿瘤性疾病患者的治疗效果。
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引用次数: 0
Genetic insights into Tietz albinism-deafness syndrome: A new dominant-negative mutation in MITF 蒂茨白化病-耳聋综合征的遗传学研究:MITF 的一种新显性阴性突变。
IF 4.3 3区 医学 Q1 Medicine Pub Date : 2024-03-04 DOI: 10.1111/pcmr.13166
Kohei Yamamoto, Ken Okamura, Kazumasa Wakamatsu, Shosuke Ito, Kozue Akabane, Yosuke Arai, Junnosuke Kawaguchi, Yutaka Hozumi, Tamio Suzuki

Tietz albinism-deafness syndrome (TADS) is a rare and severe manifestation of Waardenburg syndrome that is primarily linked to mutations in MITF. In this report, we present a case of TADS resulting from a novel c.637G>C mutation in MITF (p.Glu213Gln; GenBank Accession number: NM_000248). A 3-year-old girl presented with congenital generalized hypopigmentation of the hair, skin, and irides along with complete sensorineural hearing loss. Histopathological and electron microscopy investigations indicated that this variant did not alter the number of melanocytes in the skin but significantly impaired melanosome maturation within melanocytes. Comprehensive melanin analysis revealed marked reductions in both eumelanin (EM) and pheomelanin (PM) rather than changes in the EM-to-PM ratio observed in oculocutaneous albinism. We conducted an electrophoretic mobility shift assay to investigate the binding capability of the identified variant to DNA sequences containing the E-box motif along with other known variants (p.Arg217del and p.Glu213Asp). Remarkably, all three variants exhibited dominant-negative effects, thus providing novel insights into the pathogenesis of TADS. This study sheds light on the genetic mechanisms underlying TADS and offers a deeper understanding of this rare condition and its associated mutations in MITF.

蒂茨白化病-失聪综合征(TADS)是瓦登堡综合征的一种罕见而严重的表现,主要与 MITF 的突变有关。在本报告中,我们介绍了一例因 MITF 的新型 c.637G>C 突变(p.Glu213Gln;GenBank 编号:NM_000248)而导致的 TADS 病例。一名 3 岁女孩出现先天性全身毛发、皮肤和虹膜色素沉着,并伴有完全性感音神经性听力损失。组织病理学和电子显微镜检查表明,这种变异并没有改变皮肤中黑色素细胞的数量,但却严重影响了黑色素细胞内黑色素小体的成熟。综合黑色素分析表明,黑素(EM)和黑褐素(PM)均明显减少,而不是眼部白化病中观察到的EM-PM比例变化。我们进行了电泳迁移试验,研究已鉴定变体与含有 E-box motif 的 DNA 序列以及其他已知变体(p.Arg217del 和 p.Glu213Asp)的结合能力。值得注意的是,这三个变异体都表现出显性负效应,从而为 TADS 的发病机制提供了新的见解。这项研究揭示了 TADS 的遗传机制,加深了人们对这种罕见疾病及其相关 MITF 突变的理解。
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引用次数: 0
Topical antibiotics limit depigmentation in a mouse model of vitiligo 局部抗生素可限制白癜风小鼠模型的脱色。
IF 3.9 3区 医学 Q2 CELL BIOLOGY Pub Date : 2024-03-04 DOI: 10.1111/pcmr.13164
Ahmed Ahmed Touni, Rachel Sohn, Cormac Cosgrove, Rohan S. Shivde, Emilia R. Dellacecca, Rasha T. A. Abdel-Aziz, Kettil Cedercreutz, Stefan J. Green, Hossam Abdel-Wahab, I. Caroline Le Poole

Oral neomycin administration impacts the gut microbiome and delays vitiligo development in mice, and topical antibiotics may likewise allow the microbiome to preserve skin health and delay depigmentation. Here, we examined the effects of 6-week topical antibiotic treatment on vitiligo-prone pmel-1 mice. Bacitracin, Neosporin, or Vaseline were applied to one denuded flank, while the contralateral flank was treated with Vaseline in all mice. Ventral depigmentation was quantified weekly. We found that topical Neosporin treatment significantly reduced depigmentation and exhibited effects beyond the treated area, while Bacitracin ointment had no effect. Stool samples collected from four representative mice/group during treatment revealed that Neosporin treatment aligned with reduced abundance of the Alistipes genus in the gut, while relevant changes to the skin microbiome at end point were less apparent. Either antibiotic treatment led to reduced expression of MR1, potentially limiting mucosal-associated invariant T-cell activation, while Neosporin-treated skin selectively revealed significantly reduced CD8+ T-cell abundance. The latter finding aligned with reduced expression of multiple inflammatory markers and markedly increased regulatory T-cell density. Our studies on favorable skin and oral antibiotic treatment share the neomycin compound, and in either case, microbial changes were most apparent in stool samples. Taken together, neomycin-containing antibiotic applications can mediate skin Treg infiltration to limit vitiligo development. Our study highlights the therapeutic potential of short-term antibiotic applications to limit depigmentation vitiligo.

口服新霉素会影响小鼠的肠道微生物群并延缓白癜风的发展,而局部使用抗生素同样可以使微生物群保持皮肤健康并延缓脱色。在这里,我们研究了对易患白癜风的 pmel-1 小鼠进行 6 周局部抗生素治疗的效果。将杆菌肽、新孢子菌素或凡士林涂抹在一只脱色小鼠的侧腹上,同时用凡士林处理所有小鼠的对侧侧腹。每周对腹侧色素沉着进行量化。我们发现,局部新孢子菌素治疗可显著减少色素沉着,并在治疗区域外显示出效果,而百雀羚软膏则没有效果。在治疗过程中,从每组四只具有代表性的小鼠身上采集的粪便样本显示,新孢子菌治疗与肠道中Alistipes属丰度的降低相一致,而皮肤微生物组在终点时的相关变化则不太明显。任何一种抗生素治疗都会导致MR1表达减少,从而可能限制粘膜相关不变T细胞的活化,而新孢子菌素处理过的皮肤则选择性地显示CD8+ T细胞丰度显著降低。后一项发现与多种炎症标志物表达减少和调节性 T 细胞密度明显增加相一致。我们对良好皮肤和口服抗生素治疗的研究都使用了新霉素化合物,在这两种情况下,粪便样本中的微生物变化都最为明显。综上所述,应用含新霉素的抗生素可以介导皮肤Treg浸润,从而限制白癜风的发展。我们的研究强调了短期应用抗生素限制脱色性白癜风的治疗潜力。
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引用次数: 0
Emerging therapeutic strategies for metastatic uveal melanoma: Targeting driver mutations 转移性葡萄膜黑色素瘤的新兴治疗策略:靶向驱动突变。
IF 4.3 3区 医学 Q1 Medicine Pub Date : 2024-02-27 DOI: 10.1111/pcmr.13161
Xiao-lian Liu, Zhou Run-hua, Jing-xuan Pan, Zhi-jie Li, Le Yu, Yi-lei Li

Uveal melanoma (UM) is the most common primary malignant intraocular tumor in adults. Although primary UM can be effectively controlled, a significant proportion of cases (40% or more) eventually develop distant metastases, commonly in the liver. Metastatic UM remains a lethal disease with limited treatment options. The initiation of UM is typically attributed to activating mutations in GNAQ or GNA11. The elucidation of the downstream pathways such as PKC/MAPK, PI3K/AKT/mTOR, and Hippo-YAP have provided potential therapeutic targets. Concurrent mutations in BRCA1 associated protein 1 (BAP1) or splicing factor 3b subunit 1 (SF3B1) are considered crucial for the acquisition of malignant potential. Furthermore, in preclinical studies, actionable targets associated with BAP1 loss or oncogenic mutant SF3B1 have been identified, offering promising avenues for UM treatment. This review aims to summarize the emerging targeted and epigenetic therapeutic strategies for metastatic UM carrying specific driver mutations and the potential of combining these approaches with immunotherapy, with particular focus on those in upcoming or ongoing clinical trials.

葡萄膜黑色素瘤(UM)是成人最常见的原发性眼内恶性肿瘤。虽然原发性 UM 可以得到有效控制,但很大一部分病例(40% 或更多)最终会发生远处转移,常见于肝脏。转移性 UM 仍是一种致命疾病,治疗方案有限。UM 的发生通常归因于 GNAQ 或 GNA11 的激活突变。对 PKC/MAPK、PI3K/AKT/mTOR 和 Hippo-YAP 等下游通路的阐明提供了潜在的治疗靶点。BRCA1 相关蛋白 1(BAP1)或剪接因子 3b 亚基 1(SF3B1)的并发突变被认为是获得恶性潜能的关键。此外,在临床前研究中,已经发现了与 BAP1 缺失或致癌突变 SF3B1 相关的可操作靶点,为 UM 治疗提供了有希望的途径。本综述旨在总结针对携带特定驱动基因突变的转移性 UM 的新兴靶向和表观遗传学治疗策略,以及将这些方法与免疫疗法相结合的潜力,并特别关注那些即将或正在进行的临床试验。
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引用次数: 0
The Yucatan miniature swine as a model for post-inflammatory hyperpigmentation 将尤卡坦微型猪作为炎症后色素沉着的模型。
IF 4.3 3区 医学 Q1 Medicine Pub Date : 2024-02-16 DOI: 10.1111/pcmr.13162
Ying Wang, Emilee Herringshaw, R. Rox Anderson, Joshua Tam

Post-inflammatory hyperpigmentation (PIH) is a hypermelanosis that often occurs secondary to skin irritation or injury, especially in darker skin tones, for which there is currently a lack of effective treatment options. Few preclinical models are available to study PIH. Here, we show that the Yucatan miniature pig consistently develops PIH after skin injuries. Skin wounds were produced on Yucatan pigs by needle punches, full-thickness excisions, or burns. Wound sites were monitored and photographed regularly. Tissue samples were collected after 24 weeks and processed for histology/immunohistochemistry. Skin pigmentation and histologic changes were quantified by computer-assisted image analyses. All injury methods resulted in hyperpigmentation. Melanin content at the histologic level was quantified in the larger (burn and excision) wounds, showing a significant increase compared to uninjured skin. Increased melanin was found for both epidermal and dermal regions. Dermal melanin deposits were primarily clustered around the papillary vasculature, and were associated not with melanocytes but with leukocytes. The Yucatan miniature pig model recapitulates key clinical and histologic features of PIH in humans, including skin hyperpigmentation at both gross and histologic levels, and persistence of dermal melanin subsequent to injury. This model could be used to further our understanding of the etiology of PIH, and for new therapy development.

炎症后色素沉着(PIH)是一种过度黑色素沉着症,通常继发于皮肤刺激或损伤,尤其是肤色较深的人,目前尚缺乏有效的治疗方案。目前研究 PIH 的临床前模型寥寥无几。在这里,我们发现尤卡坦微型猪在皮肤受伤后会持续出现 PIH。尤卡坦猪的皮肤伤口是通过针刺、全厚切除或烧伤造成的。对伤口部位进行监测并定期拍照。24 周后收集组织样本并进行组织学/免疫组化处理。皮肤色素沉着和组织学变化通过计算机辅助图像分析进行量化。所有损伤方法都会导致色素沉着。与未受伤的皮肤相比,大面积(烧伤和切除)伤口的黑色素含量在组织学水平上有显著增加。表皮和真皮区域的黑色素都有所增加。真皮黑色素沉积主要聚集在乳头血管周围,与黑色素细胞无关,而是与白细胞有关。尤卡坦微型猪模型再现了人类 PIH 的主要临床和组织学特征,包括大体和组织学层面的皮肤色素沉着,以及损伤后真皮黑色素的持续存在。该模型可用于进一步了解 PIH 的病因并开发新的疗法。
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引用次数: 0
Review: Are moles senescent? 回顾:痣会衰老吗?
IF 4.3 3区 医学 Q1 Medicine Pub Date : 2024-02-15 DOI: 10.1111/pcmr.13163
Dorothy C. Bennett

Melanocytic nevi (skin moles) have been regarded as a valuable example of cell senescence occurring in vivo. However, a study of induced nevi in a mouse model reported that the nevi were arrested by cell interactions rather than a cell-autonomous process like senescence, and that size distributions of cell nests within nevi could not be accounted for by a stochastic model of oncogene-induced senescence. Moreover, others reported that some molecular markers used to identify cell senescence in human nevi are also found in melanoma cells—not senescent. It has thus been questioned whether nevi really are senescent, with potential implications for melanoma diagnosis and therapy. Here I review these areas, along with the genetic, biological, and molecular evidence supporting senescence in nevi. In conclusion, there is strong evidence that cells of acquired human benign (banal) nevi are very largely senescent, though some must contain a minor non-senescent cell subpopulation. There is also persuasive evidence that this senescence is primarily induced by dysfunctional telomeres rather than directly oncogene-induced.

黑素细胞痣(皮肤痣)一直被认为是体内细胞衰老的一个重要例子。然而,一项在小鼠模型中对诱导痣进行的研究报告称,痣是通过细胞相互作用而不是像衰老那样的细胞自主过程停止生长的,而且痣内细胞巢的大小分布无法用癌基因诱导衰老的随机模型来解释。此外,还有人报告说,用于识别人类痣中细胞衰老的一些分子标记也存在于黑色素瘤细胞中,而不是衰老细胞中。因此,有人质疑痣是否真的衰老,这对黑色素瘤的诊断和治疗具有潜在影响。在此,我将回顾这些领域,以及支持痣衰老的遗传学、生物学和分子证据。总之,有强有力的证据表明,获得性人类良性(平庸)痣的细胞在很大程度上是衰老的,尽管有些痣中一定含有少量非衰老细胞亚群。还有令人信服的证据表明,这种衰老主要是由功能失调的端粒诱发的,而不是直接由癌基因诱发的。
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引用次数: 0
Vitiligo non-responding lesions to narrow band UVB have intriguing cellular and molecular abnormalities that may prevent epidermal repigmentation 对窄波段紫外线无反应的白癜风皮损有令人费解的细胞和分子异常,这可能会阻碍表皮再色素化。
IF 4.3 3区 医学 Q1 Medicine Pub Date : 2024-02-11 DOI: 10.1111/pcmr.13160
Nathaniel B. Goldstein, Andrea Steel, Landon Tomb, Zachary Berk, Junxiao Hu, Velmurugan Balaya, Laura Hoaglin, Kavya Ganuthula, Meet Patel, Erica Mbika, William A. Robinson, Dennis R. Roop, David A. Norris, Stanca A. Birlea

We have discovered that human vitiligo patients treated with narrow-band UVB (NBUVB) demonstrated localized resistance to repigmentation in skin sites characterized by distinct cellular and molecular pathways. Using immunostaining studies, discovery-stage RNA-Seq analysis, and confirmatory in situ hybridization, we analyzed paired biopsies collected from vitiligo lesions that did not repigment after 6 months of NBUVB treatment (non-responding) and compared them with repigmented (responding) lesions from the same patient. Non-responding lesions exhibited acanthotic epidermis, had low number of total, proliferative, and differentiated melanocyte (MC) populations, and increased number of senescent keratinocytes (KCs) and of cytotoxic CD8+ T cells as compared with responding lesions. The abnormal response in the non-responding lesions was driven by a dysregulated cAMP pathway and of upstream activator PDE4B, and of WNT/β-catenin repigmentation pathway. Vitiligo-responding lesions expressed high levels of WNT10B ligand, a molecule that may prevent epidermal senescence induced by NBUVB, and that in cultured melanoblasts prevented the pro-melanogenic effect of α-MSH. Understanding the pathways that govern lack of NBUVB-induced vitiligo repigmentation has a great promise in guiding the development of new therapeutic strategies for vitiligo.

我们发现,接受窄波段紫外线照射(NBUVB)治疗的人类白癜风患者在皮肤部位表现出局部的抗再色素沉着能力,这些皮肤部位具有不同的细胞和分子通路特征。通过免疫染色研究、发现阶段 RNA-Seq 分析和原位杂交确证,我们分析了从接受 NBUVB 治疗 6 个月后未再色素沉着(无反应)的白癜风皮损处采集的配对活检组织,并将其与来自同一患者的再色素沉着(有反应)皮损进行了比较。与有反应的皮损相比,无反应的皮损表皮呈黄褐色,黑素细胞(MC)总数、增殖和分化数量较低,衰老角质细胞(KC)和细胞毒性 CD8+ T 细胞数量增加。无反应皮损的异常反应是由 cAMP 通路和上游激活剂 PDE4B 以及 WNT/β-catenin 重着色通路失调驱动的。黄褐斑反应性病变表达高水平的 WNT10B 配体,这种分子可防止 NBUVB 诱导的表皮衰老,在培养的黑色素母细胞中可防止 α-MSH 的促黑色素生成作用。了解NBUVB诱导的白癜风再色素生成缺乏的途径,对于指导开发新的白癜风治疗策略大有希望。
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引用次数: 0
The 20th International Congress of the Society for Melanoma Research 第 20 届国际黑色素瘤研究学会大会。
IF 4.3 3区 医学 Q1 Medicine Pub Date : 2024-01-11 DOI: 10.1111/pcmr.13152
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引用次数: 0
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Pigment Cell & Melanoma Research
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